McDonald was elected as a Democrat to the Thirty-first Congress, serving from March 4, 1849, to March 3, 1851. He was not a candidate for renomination in 1850, and was elected Indiana Attorney General in 1856 and was reelected in 1858. In 1859, He moved to Indianapolis in 1859, where he formed a law partnership with former Indiana Supreme Court Justice Addison Roache. He was an unsuccessful candidate for Governor of Indiana in 1864, and was elected to the United States Senate and served from March 4, 1875, to March 3, 1881. He was an unsuccessful candidate for reelection. While in the Senate he was chairman of the Committee on Public Lands (Forty-sixth Congress). McDonald sought his party's nomination for U.S. President at the 1884 Democratic National Convention in Chicago, but was defeated by New York GovernorGrover Cleveland.[1]
McDonald died in Indianapolis in 1891; interment was in Crown Hill Cemetery.