Rice is an important human staple food vulnerable to heavy metal contamination due to its unique physiology and growth environment. High yield with low heavy metal contamination is a common but highly challenging goal for rice breeders worldwide due to lack of genetic knowledge. In this report, a comprehensive GWAS analyses for ionomic and agronomic traits based on 3,259,478 SNPs were performed using two univariate methods and two multivariate methods. Under the criterium p-value <1.53×10-8, 106, 47, and 97 QTLs were identified for ionomics in flooded environment, unflooded environment, and agronomic traits, respectively. Detailed analysis of the QTLs revealed that many of the identified QTLs are co-localized with the QTLs reported in prior ionomic and agronomic studies or posited near the genes with known functions in the related traits, suggesting that our GWAS analyses are reliable. Our results further showed that each of the four GWAS methods can identify unique as well as common QTLs. When univariate methods failed to identify QTLs for a trait, the multivariate methods frequently detected QTLs. However, when many QTLs were detected by univariate methods, the number of QTLs detected by multivariate methods were reduced in many cases. These analyses suggest that using multiple GWAS methods can complement each other in QTL identification and some methods may be more powerful with less false discovery rate. In addition, several candidate genes involved in ionomic and agronomic traits control were identified by sequence analysis of the QTL regions. This research provides novel insights into the genetic basis of both ionomic and agronomic variations in rice, establishing an important foundation for further studies on reducing heavy-metal contamination and improving crop yields.