It was designed by Harry Wheelock and constructed in 1908 by T. C. Thompson for General Louis Clark. He expected the building to house Drennen's Department Store, but no agreement was reached and the space was subdivided for smaller shops. The property remained in his family for generations.
The building housed the Birmingham Press Club, and later a ballet school, on the second floor. The ground floor space housed Smith & Hardwick book store, while the basement was home to Cafe Italiano and its Piccolino Lounge.
In the early 1980s, all of Block 60 was considered for redevelopment under the Downtown Master Plan created for the city by Pedro Costa and Angelos Demetriou. Developer Raymond Gotlieb's Metropolitan Development Inc. entered into an agreement with the city to construct a 28-story Westin Hotel and office complex on the block, but was never able to secure options on enough of the land to proceed. The possibility of condemning property for redevelopment was debated in the Birmingham City Council, but was not pursued. Nevertheless, the threat led owners, the Noland Family Trust, to decline long-term leases and prompted tenants to seek new locations. The building became vacant by 1986 when the high-rise SouthTrust Tower opened across the alley.
The Clark Building was slated for demolition in the mid 1990s, but was saved by the efforts of Richard Arrington Jr, John Lauriello and Bob Moody, along with Operation New Birmingham. They recruited the law firm of Lightfoot, Franklin & White to purchase the building and renovate it as their headquarters offices. The renovations, aimed at restoring the building's historic appearance, were completed in 1998 by the Charles & Vinzant Construction Company.
- 400-410 20th Street North
- 400: former location of Industrial Savings Bank (1926-1929), Schwobilt Clothes (1964), Central Bank (-1983)
- 400½: former location of Mary Beard's Tea Room, Café Italiano (1966-1974), TC's Restaurant, Piccolino Lounge, Uptown Downtown (1981-1982)
- 402: former location of 20th Street Fruit Store, Delight Barber Shop (W. J. Bosbonis & W. G. Choron 1926-1929), gift shop (1931), vacant (1964), Charles Arndt clothiers (-1983)
- 404: former location of the Stork Shoppe, Toledo Scale Co. / Old Dutch Ribbon & Carbon Co. (1922), Mehr's Music Store & Novelty Shop (1926-1930), furrier (1931)
- 406–408: Smith & Hardwick booksellers (1949-1990)
- 410: Claradon Hat Shop, E. & W. Dry Cleaning / Stephenson Studio (1920-1926), art supplies (1931), Statesman Barber Shop (1964), Tutwiler Drug Co. (-1983)
- 410A: former location of Vernon Harris Florist (1934-1964)
- 1922-1928 4th Avenue North
- 1922: Spivy & Johnson Portrait Co. (c. 1929)
- 1924: National Shoe Fixery (1929), Tom's Cafe & Steak House (1946), The Angus (1956), Birmingham Club for Young Executives & Professionals (1964), Cane Break Supper Club (late 1960s), Grundy's Music Room (1979-1992)
- 1926: Gregory & Blake insurance agents (c. 1929)
- 1928: former location of Industrial Savings Bank (1926-1929), Schwobilt Clothes (1964), Central Bank (-1983)
- Birmingham Club
- basement: Greenwood Cave (1922–1926), Mary Beard's Tea Room (1935–1944), Cafe Italiano (1966-1974), The Cane Break (1960s-1970s), Piccolino Lounge, Uptown Downtown (1981-1982)
- 200: National Aid & Burial Co. (1926)
- 201: Keily Studio photographers (1926)
- 202: Dictaphone Sales Co. (1926)
- 203-204: Black Finance Co. (1926)
- 205-206: E. C. Fruttiger (1926)
- 207: O. V. Hunt photographer (1926)
- 208: Southern Distributing Co. (1926)
- 209: Picard Laboratories (1926)
- 212: Alabama Geological Survey (1926)
- 214: Pittsburgh Testing Laboratory (1926)
- 221: J. C. Breeden/H. Y. Webb (1926)
- 222-223: Gerhard-Mols Tailoring Co. (1925)
- 228: Turner Studio Co. photographers (1920-1926)
- 236: Retta Dawson, dressmaker and designer (1925), Stella Lynn (1926)
- Communist Party USA District 17 offices (1937)
- Polk's Birmingham City Directory (1926) Birmingham: R. L. Polk & Co.
- "Clark Building, Fourth and 20th, to get face-lifting" (July 1962) The Birmingham News - via Birmingham Rewound
- Lauriello, John (October 2010) "The Damn Yankee that Stayed - Part 2" Jefferson County Historical Association Newsletter