He moved to Michigan in 1837 and was employed as a civil engineer in railroad work.

He was active in promoting the construction of the Detroit, Hillsdale and South Western Railroad and served as its first president.

In 1854, he defeated incumbent Democrat David A. Noble to be elected as a Republican from Michigan's 2nd congressional district to the Thirty-fourth Congress.

In 1870, he was elected to represent Michigan's 1st congressional district to the Forty-second Congress and subsequently re-elected to represent Michigan's 2nd district to the Forty-third and Forty-fourth Congresses, serving from March 4, 1871 to March 3, 1877.

In 1876, Waldron was elected president of the First National Bank of Hillsdale and served until his death.