Macnow was born in New York City, and raised in Buffalo, New York. He went to Boston University (with WIP co-worker Al Morganti), and worked a newspaper career that took him from Cocoa Beach, Florida to Fort Lauderdale, Florida to Detroit, Michigan, and, finally to the Philadelphia Inquirer in 1986. During his time with the Inquirer, in 1993, he was recognized as "The Best Sportswriter in Philadelphia" by Philadelphia magazine.

Glen is often referred to as "The Prof" or "The Professor" due to his position as an instructor on the St. Joseph's University faculty and the professorial manner with which he discusses sports topics.

Macnow has written more than a dozen children's books, mostly sports biographies. He has also written three top-selling Philadelphia sports books during his time on WIP. In 2003, he co-authored The Great Philadelphia Fan Book with Anthony Gargano. The book is a Philadelphia sports memoir, centering around the city's sports fans and 4 professional teams. In 2004, he co-authored The Great Philadelphia Sports Debate with Angelo Cataldi. In 2006, he co-authored The Great Book of Philadelphia Sports Lists with Edward Gudonis, a.k.a. Big Daddy Graham.

Macnow is known for some of his off-sports shows, including the "Movie Club for Men," a regular summer feature, and his annual "food hunt," which searches for the best of a particular manly food item (burgers, pizza, ribs, cheesesteaks, etc.) in the Delaware Valley.