Pennefather was born in Tipperary, the second son of William Pennefather of Knockeevan, member of the Irish House of Commons for Cashel and his wife Ellen Moore, daughter of Edward Moore, Archdeacon of Emly. He went to school in Clonmel and graduated from the University of Dublin. He was called to the Irish Bar in 1795. His brother Richard Pennefather had a longer and more successful career as a judge: appointed a Baron of the Court of Exchequer in 1821, he served for nearly 40 years and was held in universal regard; with the general support of the profession he remained on the Bench until shortly before his death at eighty-six, by which time he was blind. Edward and Ricahrd: "the two Pennefathers" were leading practitioners in the Court of Chancery. Edward was generally regarded as the more gifted of the two, a master of the law of equity, and also a skilled libel lawyer. In 1816 he was one of the lead counsel in the celebrated libel case of Bruce v. Grady, which arose from the publication of a scurrilous poem called "The Nosegay", written by a barrister Thomas Grady about his former friend, the notably eccentric banker George Evans Brady of Hermitage House, Castleconnell. The quarrel is said to have arisen from a dispute over money which Bruce had loaned to Grady. The plaintiff claimed £20000; the jury awarded £500.
According to Elrington Ball, Pennefather was considered to be one of the greatest Irish advocates of his time, and one with few rivals in any age, but he did not live up to expectations as a judge, due to his age and increasing ill-health. As a judge he is remembered mainly for presiding at the trial of Daniel O'Connell in 1843 for sedition, where his alleged bias against the accused damaged his reputation: he was accused of acting as prosecutor rather than judge, and his summing-up was described as simply an extra speech for the prosecution. Further damage to his reputation was done by the majority decision of the House of Lords quashing the verdict in the O'Connell case: while many of the errors were the fault of the prosecution, the Law Lords did not spare Pennefather for his conduct of the proceedings, and in particular for his summing-up. The Law Lords commented severely that the course of the trial, if condoned, would make a mockery of trial by jury in Ireland. The related trial of Sir John Grey descended into farce when the Attorney General, Sir Thomas Cusack-Smith, who was noted for his hot temper, challenged one of the defence counsel Gerald Fitzgibbon to a duel, for having allegedly accused him of improper motives. Pennefather told the Attorney General severely that a man in his position had no excuse for such conduct, whereupon the Attorney General agreed to let the matter drop.
