In 1538 he obtained a dispensation permitting him to hold a benefice, notwithstanding his being a natural son, and in June 1546 he was made an acolyte in the cathedral church of Aberdeen, of which he was afterwards appointed a canon and prebendary.

After the failure of the royal cause, and while Mary was a captive in England, Lesley (who had gone to her at Bolton) continued to exert himself on her behalf.

He appeared as her ambassador at the court of Elizabeth I to complain of the injustice done to her, and when he found he was not listened to he laid plans for her escape.

He also wrote for her use his Piae Consolationes, and the queen devoted some of the hours of her captivity to translating a portion of it into French verse.

[2] In October 1578 he had an audience with Rudolf II, Holy Roman Emperor, and their discussions included making a double portrait of Mary and James VI.

In 1593 he was made bishop of Coutances, Normandy, and had licence to hold the bishopric of Ross until he should obtain peaceable possession of the former see.

[4] The following year, his nephew and heir, also called John Lesley, dedicated an epitaph to commemorate the first anniversary of his death.

John Lesley, bishop of Ross, Scot, of the renowned Lesley family, well versed in all sorts of science, speaker for the king of France François II, counsellor to Mary ... queen of Scots, defender most constant of the catholic faith, after huge toils for the ancestral faith, in particular after having been brought back in the kingdom of Scotland after the defence in England of Mary, queen of Scots, after having accomplished many things worthy of the highest praise, died quietly in Brussels on the eve of the calends of June (= May 31) in the year 1596, aged 70.

Not to remain ungrateful to his dear uncle, John Lesley his nephew, his sad heir, had (this stone) installed and for the anniversary itself established ... in this monastery of Grenbergen on the eve of the calends of June for it to be celebrated.