He is an ecologist whose work has focused on science methodology, particularly the use of structural equation modeling as a means of investigating complex, system-level hypotheses.

This later led Grace to introduce meta-modeling to the field of statistical ecology as a means of operationalizing multi-dimensional concepts.

[10][11] His applications of these methods have spanned the range from wetlands to deserts, from the arctic to the tropics, from trophic cascades to the design of cities, and have included the effects of fires, hurricanes, and changes in climate.

[13] In 2021 he received the Presidential Rank Award, which is given out by the president of the United States and is the highest honor given to career senior scientists or other executives for the conduct of their duties.

He has published over 200 papers and reports,[14] including 3 books, one on competitive interactions, one on community analysis, and one on structural equation modeling.