About 1628 he was ordained, and, after serving curacies in and near Oxford, he was chosen in 1631 lecturer at All Hallows, Bread Street, London, where he was popular as a preacher.
For his refusal to comply with the rubrics he was suspended by William Laud, and would have emigrated to America had he not been dissuaded by John Dod, on whose recommendation he was appointed chaplain to Robert Greville, 2nd Baron Brooke at Warwick Castle.
On his deciding to leave the city the prince provided him with safe-conducts, which enabled him to travel in peace to Coventry.
For holding services in secret he was arrested in 1665 and, with his brother-in-law and assistant Thomas Martyn, confined on St. Nicholas Island for about nine months.
Friends managed to procure his release by giving security; but he was forbidden to live within twenty miles of Plymouth.
A memorial tablet was erected to him about 1670 by Thomas Crispin, for which Hughes's son-in-law John Howe wrote a Latin inscription.