Upon John Maitland's return, through the influence of his brother, William Maitland, he received the offer of the position of Commendator of Kelso Abbey, which he shortly afterwards exchanged with Francis Stewart, later Earl of Bothwell, for the Priory of Coldingham. This transaction was ratified by Mary, Queen of Scots on April 20, 1567.
Upon the death of his father, he was appointed Keeper of the Privy Seal of Scotland, on April 20, 1567. He also supported Regent Murray, and sat in his parliaments in December 1567 and August 1568. On June 2, 1568 he was created a Senator of the College of Justice as an Ordinary Lord on the spiritual side. He retained the rich endowment of Coldingham until 1570.
Following the Regent Murray's assassination, Maitland joined the Lords who met on the Queen's behalf at Linlithgow, and shared in the dangers of the civil war which ensued. At the end of 1570 he was denounced a rebel by the King's party, with his brothers William and Thomas, and they were all forfeited in the parliament which met in the Canongate, the so-called 'cropped parliament'.
John Maitland was deprived of all his offices and benefices, and took refuge in Edinburgh Castle. Upon its surrender on the 29 May 1573 he was sent as a prisoner to Tantallon Castle in Haddingtonshire. After nine months confinement there he was removed to Hugh, Lord Somerville's house of Cowthallie, under house-arrest with bail at £10,000 Scots. In 1574/5 a Letter of Rehabilitation in his favour, as "Commendator of Coldingham", passed the Great Seal.
On April 26, 1581, he was reappointed Keeper of the Privy Seal of Scotland and returned to the Bench. He was shortly afterwards made a Privy Counsellor, and upon the dismissal of Abbot Pitcairn, appointed Secretary of Scotland on May 18, 1584. In the parliament which met on the 22nd of that month his doom of forfeiture was reduced, and he was restored to all the honours, heritages, and offices he had formerly possessed. He was appointed Vice-Chancellor on 31 May 1586.
He was also appointed Lord Chancellor of Scotland in 1586, following Arran's disgrace. In 1589 a powerful combination, headed by the Earls of Huntly, Errol, and Bothwell, &c., was formed against Maitland. It was intended to meet at Quarryholes, between Leith and Edinburgh, to march in a body to Holyroodhouse, make themselves master of the King's person, and put the Chancellor to death. The King and Maitland were not, however, at Holyroodhouse and the plot failed. Several other plots were formed against him shortly afterwards, but they were all defeated.
He was one of those who accompanied James VI on his matrimonial voyage to Denmark and shortly after his return he was made a Lord of Parliament with the title Lord Maitland of Thirlestane, on May 18, 1590.
Sir John Scot of Scotstarvet, writing in 1754, had this to say of the 1st Lord Maitland: "Mr John Maitland, second brother to Secretary Maitland, after he had studied the laws in France, was preferred to be a Lord of Session by the said Earl of Arran's means, and thereafter became Chancellor. He was one of the Octavians (a name given to eight persons who managed affairs under king James VI), and was created Lord Thirlestane (sic), and was an excellent Latin poet, as his verses inserted in Deliciae poetarum scotorum testify; and King James had such a respect to him, that he made the epitaph engraven on his tomb. Yet the conquest he made of the barony of Liddington (Lethington) from his brother's son, James Maitland, was not thought lawful nor conscientious."
He was buried in St. Mary's, Haddington, where a splendid monument, with an epitaph, composed by King James VI, was erected to his memory. The Commendatorship of Coldingham was bestowed upon Francis Stewart, 1st Earl of Bothwell, eldest son of the late Prior, John Stewart.
The 1st Lord Maitland of Thirlestane had married Jean (1554 - 1609), daughter of James, 4th Lord Fleming. They had two children: Anne (1589 - 1609) who married Robert Seton, 2nd Earl of Winton (but had no issue), and the heir and successor John Maitland, 1st Earl of Lauderdale, &c.