Thomas was the son of Thomas Senior, a younger son of Sir Robert de la Mare of Aldermaston House in Berkshire. Nothing is known of his mother, but his paternal grandmother was Katherine, the eldest daughter of Sir Bernard Brocas Junior of Clewer and Beaurepaire (Sherborne St. John) who was executed for his role in the Earl's Revolt against King Henry IV. The Berkshire De la Mares were probably a branch of the same family from Steeple Lavington in Wiltshire.

Thomas' father died when he was still a youngster and he and his two sisters were brought up in his grandfather's household (a third sister died young). Sir Robert himself died in 1431 and, his eldest son, Richard, also having predeceased him,  the De la Mare estates of Aldermaston, Sparsholt, Colthrop and West Court (Finchampstead) were all inherited by the eleven-year-old Thomas. His wardship and marriage rights were granted to a certain Richard Melbourne and he did not take full possession of his manors until his marriage to Elizabeth, the daughter of William Fynderne of Childrey in 1449.

Thomas was now an important landowner and, the following year, he was appointed as one of the commissioners for Berkshire sent out to collect a subsidy for the defence of the Realm. He then became Justice of the Peace for the county in 1454 and, again, in 1456. The following year, he was admitted to Lincoln's Inn, as well as "to all repasts when Lord or Lady Buckingham, or the Earl of Stafford, or Henry Stafford should be in London or Westminster". Thus, it appears that Thomas was, at an early date, enjoying the patronage of the great House of Stafford.

In 1457 & 8, Thomas was serving as a commissioner of array for Berkshire, and the following year became  Sheriff for Oxfordshire and Berkshire too. Such high positions led him to become embroiled in the movements of the War of the Roses and, on 21st December 1459, he was ordered (with others) "to resist the rebellion of Richard, Duke of York ... attainted of high treason". The following year, he was to call arms "all persons in the county of Berkshire able to labour" to resist the Duke and his party "as soon as they hear that they enter the realm". At the end of June the following year, York's son, Edward, and his in-laws, the Earls of Salisbury and Warwick were marching on the Capital, and Thomas felt it wise to seek refuge in the Tower of London, along with his friends, the Lords Hungerford and Scales, who had not long returned from routing out Yorkists in Newbury. Perhaps Thomas had helped them there.

Hungerford and Scales surrendered the Tower soon after the Lancastrian defeat at Battle of Northampton only a month later. They were allowed to depart while Thomas was taken as prisoner by Lord Wenlock. He thus missed out the death of York, the declaration of his son as Edward IV and the expulsion of King Henry. He was pardoned, along with many other Lancastrians in February 1462 and quickly returned to more local  affairs around his home. He served as JP for Berkshire between 1463 & 7, and was appointed Sheriff of Wiltshire in 1465. But it seems that Thomas could not let go of his Lancastrian loyalties. As early as July 1469, the Patent rolls refer to him as "late of Aldermaston, co. Berks, esquire" suggesting that he had already been turfed out of Aldermaston house for joining the Earl of Warwick's revolution to re-instate Henry VI. This was, of course, only briefly successful but, during that period, Thomas did serve on the Commission of the Peace for Berkshire. In April 1471 however, King Edward IV returned from exile, Warwick was killed at the Battle of Barnet and, a month later, Henry VI was also dead. By February 1472, Thomas de la Mare required a second pardon from the King.

Thomas seems to have now become reconciled to the new Yorkist regime. In the same year as his pardon, when troubles in Brittany made it prudent to summon another commission of array for Berkshire, Thomas was again one of the appointed commissioners. While, in the October Parliament summoned by King Edward to grant his finances the French Wars, Thomas sat as MP for Berkshire. In 1473, he celebrated the marriage of his eldest son, John, to the daughter of Thomas D'Abridgecourt of Stratfield Saye (Hampshire) by settling Aldermaston on them as part of their marriage settlement. By 1475, Thomas had been knighted and he took up the post of Sheriff of Oxfordshire and Berkshire again (and once more in 1480). Over the next eight years, he appeared on numerous Berkshire commissions and, in Apri1 1483, he was required to "to assess certain subsidies granted to the late King [Edward IV] by the Commons of the Realm" in Berkshire. In the August, Thomas was again "to assess certain subsidies and appoint collectors of the same" for the new king, Richard III.

However, like his relative, Sir William Norreys of Yattendon Castle - with whom he he was often associated in his commissions - Sir Thomas seems to have become disaffected with the new monarch. Perhaps through such ties of kinship, fears for his livelihood, personal hostility to members of Richard II's inner circle or even commercial considerations, he reverted to his Lancastrian sympathies by joining the Duke of Buckingham's Rebellion in a failed attempt to overthrow the King. On 18th October that same year, while the Duke assembled his forces at Brecon, Sir Thomas and Sir William, along with other leading men of the day, gathered further rebels at Newbury and declared the Earl of Richmond - the last Lancastrian heir - as King. Unfortunately, support for the rising quickly fell away and Buckingham was captured and executed. 

Sir Thomas was attainted by the 1484 Parliament as one of the "false traitors and rebels" gathered at Newbury, but he escaped further degradation by fleeing to the sanctuary of Sion Abbey (Middlesex), where he appears to have taken up his abode. He was, however, pardoned in the April of that year, although he may not have been allowed to leave the monastic enclave for, in February 1485, it is recorded that his friends were allowed to supply him with food without fear of incurring the Royal displeasure. He appears to have resumed his life in the outside World after Richmond took the Throne as King Henry VII in 1485 and, the following year, was commissioned to round up a number of outlaws and felons. 

Despite this re-emergence, Sir Thomas’ will, dated 1490, refers to his "great sorrows and losses" and also as to the possibility of being unable to pay his debtors in full. This he deplored and so begged that he would be leniently dealt with. He directed his body to be buried in the church at Sion, before the Crucifix, or where it may please the Abbess and Master Confessor. Sir Thomas died on 2nd September 1492 when his estates were inherited by his fourteen-year-old grandson, also named Thomas.