The regiment took part in 29 battles and four sieges in a variety of theaters of the war. After their early service at Fortress Monroe in Virginia, the 29th was attached, in the spring of 1862, to the Army of the Potomac during the Peninsular Campaign as part of the famed Irish Brigade. The 29th had the distinction of being the only regiment of non-Irish ethnicity to serve in that brigade. In January 1863, the IX Corps (including the 29th Massachusetts) was transferred to Kentucky and engaged in operations against Confederate guerillas. In the summer of 1863, the IX Corps was again transferred and took part in the siege of Vicksburg and the siege of Jackson, Mississippi. In the fall of 1863, IX Corps took part in the Knoxville Campaign which resulted in the defeat of Confederate forces in eastern Tennessee. The spring of 1864 saw the IX Corps and the 29th Massachusetts once again returned to duty with the Army of the Potomac, just in time to take part in the Overland campaign and the siege of Petersburg. During the siege of Petersburg, the unit suffered their worst casualties of the war in the Battle of Fort Stedman on March 25, 1865.