In January 1643, Colonel Oliver Cromwell was promoted to the rank of captain, which released him from the command of the Earl of Essex. He was assigned to aid Lord Grey of Warke, commander of the newly formed military alliance called the Eastern Association. The Eastern Association consisted of the armies raised in many of the counties east of London, where support for Parliament's cause against King Charles I was strong. The goal of the Eastern Association was to rid its member counties of Royalists. As captain of a regiment that came to be known as the "Ironsides," Cromwell led his men to military victories at the northern frontier of the Eastern Association counties. Between April twenty-three and twenty-eight, 1643, Cromwell's men besieged the Royalist forces at Crowland Abbey, which they then made a parliamentary possession. Cromwell's successes at the battlefield at Lincolnshire and in numerous skirmishes against Royalist garrisons in 1643 were also an important of the Eastern Association's efforts.

Whenever his men were successful in achieving their military objectives, Cromwell attributed their success to God's assistance of their cause. Cromwell felt that his military mission was also a religious quest to defend God's church in England from Catholic corruption. Cromwell's great zeal had a contagious effect on his men. As a military leader, Cromwell imposed an exceptionally disciplined regimen on his men. Cromwell's regiment was perhaps the best trained in all of England, and Cromwell's men feared him greatly. Despite the harsh discipline, which included public whippings for desertion attempts, most of Cromwell's soldiers admired and respected him. Cromwell was also very hostile toward professional soldiers–officers from the English noble classes who often received their commissions because they belonged to the right families rather than because of their merit as soldiers. Cromwell irritated many of his superiors with his confidence in the leadership abilities of men from the middle-class, and with his habit of conferring promotions only on those soldiers who proved their abilities on the battlefield.

Despite their early successes in 1643, Parliament's armies suffered a number of heavy losses in the second half of the year. Cromwell himself experienced some minor losses, and he grew rather anxious with the overall situation. He blamed the poor outlook of the war on his own commanders, who he thought were fighting too indifferently to be victorious, and grew angry at Parliament, which he believed was not doing enough to support its troops. By November 1643, the money for supplying Parliamentary troops was drying up and the situation became so desperate that Cromwell, along with his new senior commander, Lord Manchester, went to London to demand more support.

While in London, Cromwell proved himself more adept than he had ever been at political maneuvering. In January 1644 Parliament appointed him Lieutenant- General of the Easter Association, making him second-in-command to Manchester. The following month, Cromwell was appointed a member of the newly formed parliamentary Committee of Both Kingdoms. This appointment was a way of recognizing Cromwell for his proven leadership in the Civil War.

In July two, 1644, Cromwell's cavalry troops were largely responsible for the Parliamentary army's first great victory at the battle of Marston Moor. Cromwell's leadership was a decisive factor in the victory, and his reputation as a leader began to spread beyond the military and parliamentary circles and into the popular imagination. Newspapers in London hailed him as the divinely appointed savior of England. By the winter of 1644–1645, Cromwell had become a pivotal figure in Parliament, to which he returned to resolve the recent political falling-out he had had with Manchester and some of the other commanders. Cromwell had strong disagreements with these commanders about how the war should be fought, and they further disliked him for his rather unorthodox disdain for the English nobility. On December nine, Cromwell delivered a very powerful speech to the House of Commons, urging greater commitment to the cause of victory. "If the Army be not put into another method," he warned, "and the war more vigorously prosecuted, the people can bear the war no longer, and will force you to a dishonourable peace."

Cromwell and his friends in Parliament were able to marshal the political momentum necessary to push through a bill called the Self-Denying Ordinance. This Ordinance made it illegal for members of Parliament to hold army commands. It was a brilliant political move which had the effect of sidestepping all of the problematic infighting among the various Parliamentary leaders in the war. Taking command out of the hands of Manchester, Essex, and Sir William Waller, it united their armies into one New Model Army under the command of a certain Lord Fairfax. Cromwell himself was granted exemption from the Ordinance, and was made second-in-command to Fairfax as Lieutenant-General of the New Model Army.

Parliament's victory in the English Civil War was sealed in 1645, first with New Model Army's defeat of the Royalists at Naseby, then with their victory at Langport. The Battle of Naseby, which was fought on June fourteen, 1645, was a crushing defeat for the Royalists and a stunning victory for Cromwell. The Battle of Langport was the last major battle of the war. Minor fighting continued until May of the following year, when the war officially ended. As the end approached, Cromwell began to call for greater political unity in Parliament. Many MPs resented Cromwell's appeal for cooperation, but Cromwell's crucial role in the outcome of the Civil War meant that it was no longer possible for him to be ignored.

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