In 1834 Cockburn was well enough thought of to be made a member of the commission to inquire into the state of the corporations of England and Wales. Other parliamentary work followed; but he had ambition to be more than a parliamentary counsel, and attended diligently on his circuit, besides appearing before committees. In 1841 he was made a Q.C., and in that year a charge of simony, brought against his uncle, William, dean of York, enabled him to appear conspicuously in a case which attracted considerable public attention, the proceedings taking the form of a motion for prohibition duly obtained against the ecclesiastical court, which had deprived Dr Cockburn of his office. Not long after this, Sir Robert Peel's secretary, Edward Drummond, was shot by the crazy Scotsman, Daniel M'Naughten, and Cockburn, briefed on behalf of the assassin, not only made a very brilliant speech, which established the defence of insanity, but also secured the full publicity of a long report in the _Morning Chronicle_ of the 6th of March 1843. Another well-known trial in which he appeared a year later was that of _Wood_ v. _Peel_ (_The Times_, 2nd and 3rd of July 1844), the issue being in form to determine the winner of a bet (the Gaming Act was passed in the following year) as to the age of the Derby winner Running Rein--in substance to determine, if possible, the vexed question whether Running Rein was a four-year-old or a three-year-old when he was racing as the latter. Running Rein could not be produced by Mr Wood, and Baron Alderson took a strong view of this circumstance, so that Cockburn found himself on the losing side, while his strenuous advocacy of his client's cause had led him into making, in his opening speech, strictures on Lord George Bentinck's conduct in the case which had better have been reserved to a later stage. He was, however, a hard fighter, but not an unfair one--a little irritable at times, but on the whole a courteous gentleman, and his practice went on increasing.
In 1847 he decided to stand for parliament, and was elected without a contest Liberal M.P. for Southampton. His speech in the House of Commons on behalf of the government in the Don Pacifico dispute with Greece commended him to Lord John Russell, who appointed him solicitor-general in 1850 and attorney-general in 1851, a post which he held till the resignation of the ministry in February 1852. During the short administration of Lord Derby which followed, Sir Frederic Thesiger was attorney-general, and Cockburn was engaged against him in the case of _R._ v. _Newman_, on the prosecution of Achilli. This was the trial of a criminal information for libel filed against John Henry Newman, who had denounced a scandalous and profligate friar named Achilli, then lecturing on Roman Catholicism in England. Newman pleaded justification; but the jury who heard the case in the Queen's Bench, with Lord Campbell presiding, found that the justification was not proved except in one particular: a verdict which, together with the methods of the judge and the conduct of the audience, attracted considerable comment. The verdict was set aside, and a new trial ordered, but none ever took place. In December 1852, under Lord Aberdeen's ministry, Cockburn became again attorney-general, and so remained until 1856, taking part in many celebrated trials, such as the Hopwood Will Case in 1855, and the Swynfen Will Case, but notably leading for the crown in the trial of William Palmer of Rugeley in Staffordshire--an ex-medical man who had taken to the turf, and who had poisoned a friend of similar pursuits named Cook with strychnine, in order to obtain money from his estate by forgery and otherwise. Cockburn made an exhaustive study of the medical aspects of the case, and the prisoner's comment when convicted after a twelve days' trial was, alluding to the attorney-general's advocacy, "It was the riding that did it." In 1854 Cockburn was made recorder of Bristol. In 1856 he became chief justice of the common pleas. He inherited the baronetcy in 1858. In 1859 Lord Campbell became chancellor, and Cockburn became chief justice of the Queen's Bench, continuing as a judge for twenty-four years and dying in harness. On Friday, the 19th of November 1880, he tried causes with special juries at Westminster; on Saturday, the 20th, he presided over a court for the consideration of crown cases reserved; he walked home, and on that night he died of _angina pectoris_ at his house in Hertford Street.