 Upon graduating in 1899, he joined the brewery of Arthur Guinness & Son in Dublin, Ireland, where he would spend the rest of his 38-year career

Gosset had three children with Marjory Gosset (née Surtees).Harry Gosset (1907-1965) was a consultant paediatrician; Bertha Marian Gosset (1909-2004) was a geographer and nurse; the youngest, Ruth Gosset (1911-1953) married the Oxford mathematician Douglas Roaf and had five children.In his job as Head Experimental Brewer at Guinness, the self-trained Gosset developed new statistical methods – both in the brewery and on the farm – now central to the design of experiments, to proper use of significance testing on repeated trials, and to analysis of economic significance (an early instance of decision theory interpretation of statistics) and more, such as his small-sample, stratified, and repeated balanced experiments on barley for proving the best yielding varieties.