diff --git a/src/components/datagrid/body/data_grid_cell.tsx b/src/components/datagrid/body/data_grid_cell.tsx
index 30273b49fed..920736b98d2 100644
--- a/src/components/datagrid/body/data_grid_cell.tsx
+++ b/src/components/datagrid/body/data_grid_cell.tsx
@@ -400,6 +400,10 @@ export class EuiDataGridCell extends Component<
         },
         0
       );
+      // Close the cell popover if the popover was open and the user clicked the cell
+      if (this.props.popoverContext.popoverIsOpen) {
+        this.props.popoverContext.closeCellPopover();
+      }
     }
   };
 
diff --git a/src/components/datagrid/body/data_grid_cell_popover.spec.tsx b/src/components/datagrid/body/data_grid_cell_popover.spec.tsx
index 378442a66ac..f609592138e 100644
--- a/src/components/datagrid/body/data_grid_cell_popover.spec.tsx
+++ b/src/components/datagrid/body/data_grid_cell_popover.spec.tsx
@@ -83,4 +83,21 @@ describe('EuiDataGridCellPopover', () => {
         .should('have.attr', 'data-gridcell-row-index', '1');
     });
   });
+
+  it('closes the cell popover when the originating cell is clicked', () => {
+    cy.realMount(<EuiDataGrid {...baseProps} />);
+    cy.get(
+      '[data-gridcell-row-index="0"][data-gridcell-column-index="0"]'
+    ).realClick();
+
+    cy.get('[data-test-subj="euiDataGridCellExpandButton"]').realClick();
+    cy.get('[data-test-subj="euiDataGridExpansionPopover"]').should('exist');
+
+    cy.get(
+      '[data-gridcell-row-index="0"][data-gridcell-column-index="0"]'
+    ).realClick();
+    cy.get('[data-test-subj="euiDataGridExpansionPopover"]').should(
+      'not.exist'
+    );
+  });
 });
diff --git a/src/components/datagrid/body/data_grid_cell_popover.test.tsx b/src/components/datagrid/body/data_grid_cell_popover.test.tsx
index 792e74b558f..da00dc334cd 100644
--- a/src/components/datagrid/body/data_grid_cell_popover.test.tsx
+++ b/src/components/datagrid/body/data_grid_cell_popover.test.tsx
@@ -101,7 +101,6 @@ describe('useCellPopover', () => {
           hasArrow={false}
           isOpen={true}
           onKeyDown={[Function]}
-          onTrapDeactivation={[Function]}
           panelClassName="euiDataGridRowCell__popover"
           panelPaddingSize="s"
           panelProps={
diff --git a/src/components/datagrid/body/data_grid_cell_popover.tsx b/src/components/datagrid/body/data_grid_cell_popover.tsx
index 03e59a61060..32a38364aae 100644
--- a/src/components/datagrid/body/data_grid_cell_popover.tsx
+++ b/src/components/datagrid/body/data_grid_cell_popover.tsx
@@ -83,7 +83,6 @@ export const useCellPopover = (): {
         'data-test-subj': 'euiDataGridExpansionPopover',
       }}
       closePopover={closeCellPopover}
-      onTrapDeactivation={closeCellPopover}
       onKeyDown={(event) => {
         if (event.key === keys.F2 || event.key === keys.ESCAPE) {
           event.preventDefault();
diff --git a/upcoming_changelogs/5797.md b/upcoming_changelogs/5797.md
new file mode 100644
index 00000000000..3124fd3f845
--- /dev/null
+++ b/upcoming_changelogs/5797.md
@@ -0,0 +1,3 @@
+**Bug fixes**
+
+- Fixed an `EuiDataGrid` bug occurring when closing cell popovers on clicking the originating cell. The original fix was unintentionally affecting cell popovers with nested modals, popovers, etc.