Anglo-African left Cardiff on her last voyage on 17 July 1908 for Valparaiso fully laden with coal. The ship was under command of captain James Hedley Henderson and had a crew of 34. She reached her destination on August 26, and after discharging her cargo loaded almost 7,000 tons of nitrate of soda at Caleta Buena, Junín, Iquique and Tocopilla for delivery to North America. She left Tocopilla on 19 November 1908 and after largely uneventful journey arrived at Saint Lucia for coaling on December 28 and sailed the next day for Baltimore. The weather was fine and clear until the afternoon of 5 January 1909 when it first became cloudy and shortly after it started to rain. The weather progressively worsened through the evening and the late afternoon with heavy fog developing, but the ship continued on at full speed. Soundings were taken on the regular basis to ascertain the ship position relative to the coast, but no visual observations were possible due to thick weather at the time, and no lights from either Cape Henry or Cape Charles lighthouses could be seen.
